Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

Choreoathetosis in Moyamoya Disease.

Moyamoya disease is a cerebral angiopathy characterized by bilateral progressive narrowing of internal carotid arteries, developing collateral vessels with the aspect of a "puff of smoke." The presentation with movement disorders is extremely rare. We present the case of an 11-year-old girl with low academic performance who complained of involuntary movements starting in her right hand. Neurologic examination showed preserved muscle strength and right hemichoreoathetosis. Neuroimaging showed left hemisphere hypoperfusion and a hypertrophic distal lenticulostriate artery. The symptoms were controlled with medications, and cerebral revascularization was performed. Although movement disorders are usually related to cerebral lesions or hypoperfusion, cases without these etiologies were described. Thus the finding of asymmetric lenticulostriate arteries improving after asymmetry reduction suggests a possible role in the pathogenesis. Further studies are needed to fully elucidate the mechanisms between moyamoya disease and movement disorders.

Cervical Disorders in Mucopolysaccharidosis IVA-Morquio disease.

Morquio disease or mucopolysaccharidosis type IVA (Online Mendelian Inheritance in Man No. 253000) is a rare autosomal recessive disease classified in the group of metabolism inborn errors. The glycosaminoglycans accumulate in chondrocytes, which disturbs bone growth and leads to skeletal manifestations, such as skeletal dysplasia and a short stature. In addition, the disproportionate growth of the trachea can lead to airway insufficiency. We report the case of a 27-year-old man with dwarfism due to Morquio disease, which had resulted in quadriparesis, hyperreflexia, and dyspnea, requiring a "look up to the sky" compensatory position. Imaging studies of the neck showed tracheal tortuosity, spinal stenosis, myelopathy, and neurogenic arthropathy (Charcot joint). The patient was treated with occipital-cervical-thoracic instrumentation. However, postoperative tracheal correction was required. Considering the wide spectrum of clinical features in those with mucopolysaccharidosis type IVA, individualized multidisciplinary treatment is recommended.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice.

Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.

Pubertal development and adult height in patients with congenital hypothyroidism detected by neonatal screening in southern Brazil.

Objectives Adequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients. Methods Clinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls). Results Median chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 µg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04). Conclusions In this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

Postnatal management of growth failure in children born small for gestational age.

OBJECTIVES: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age. SOURCE OF DATA: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors. DATA SYNTHESIS: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period. CONCLUSIONS: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.

Postnatal management of growth failure in children born small for gestational age / Manejo pós-natal da falha de crescimento em crianças nascidas pequenas para a idade gestacional

Abstract Objectives: To discuss the etiology and growth consequences of small size at birth and the indications, effects, and safety of biosynthetic growth hormone therapy in children born small for gestational age. Source of data: A comprehensive and non-systematic search was carried out in the PubMed, LILACS, and SciELO databases from 1980 to the present day, using the terms "small for gestational age," "intrauterine growth restriction," and "growth hormone". The publications were critically selected by the authors. Data synthesis: Although the majority of children born small for gestational age show spontaneous catch-up growth during the first two years of life, some of them remain with short stature during childhood, with high risk of short stature in adult life. Treatment with growth hormone might be indicated, preferably after 2-4 years of age, in those small for gestational age children who remain short, without catch-up growth. Treatment aims to increase growth velocity and to reach a normal height during childhood and an adult height within target height. Response to growth hormone treatment is variable, with better growth response during the pre-pubertal period. Conclusions: Treatment with growth hormone in short children born small for gestational age is safe and effective to improve adult height. Efforts should be done to identify the etiology of small size at birth before treatment.

Resumo Objetivos: Discutir a etiologia e as consequências para o crescimento e as indicações, os efeitos e a segurança da terapia com hormônio de crescimento biossintético em crianças pequenas para idade gestacional. Fonte dos dados: Uma busca abrangente e não sistemática foi feita nas bases de dados PubMed, LILACS e SciELO de 1980 até a presente data, com os termos "small for gestational age" (pequeno para a idade gestacional), "intrauterine growth restriction" (restrição de crescimento intrauterino) e "growth hormone" (hormônio do crescimento). As publicações foram selecionadas criticamente pelos autores. Síntese dos dados: Embora a maioria das crianças nascidas pequenas para idade gestacional apresente recuperação espontânea do crescimento durante os dois primeiros anos de vida, algumas delas permanecem com baixa estatura durante a infância, com alto risco de baixa estatura na vida adulta. O tratamento com hormônio de crescimento pode ser indicado, preferencialmente após os dois aos quatro anos, naquelas crianças sem recuperação espontânea do crescimento e com baixa estatura. Seus objetivos são aumentar a velocidade de crescimento e atingir uma altura normal durante a infância e uma altura adulta dentro da altura-alvo. A resposta ao tratamento com hormônio de crescimento é variável, com melhor resultado se iniciado durante o período pré-puberal. Conclusões: O tratamento com hormônio de crescimento em crianças baixas nascidas pequenas para idade gestacional é seguro e eficaz para melhorar a estatura adulta. Esforços devem ser feitos para identificar a etiologia do nascimento pequenas para idade gestacional antes do tratamento.